Physiology

Pharmacokinetic and pharmacodynamic changes

Therefore, ↓ V_D for water-soluble drugs, ↑ V_D for fat-soluble drugs.

Specific drugs

Anticholinergics. Increased V_D atropine with ↑ half-life. Causes central anticholinergic syndrome unlike glycopyrrolate because of passage across blood–brain barrier.

Barbiturates. Larger V_D with prolonged clearance; 30–40% ↓ dose requirement.

Benzodiazepines (Table 6.1). Increased CNS sensitivity. High protein binding of diazepam results in greater free drug in elderly in contrast to lesser change in dose requirements of midazolam. The latter may cause severe hypotension in the elderly (Committee on Safety of Medicines warning).

Table 6.1 Half-life of benzodiazepines

Propofol. 50% reduced dose requirement. More enhanced CVS depression and greater hypotensive effect (diastolic > systolic). Reduce hypotension on induction by slower rate of injection. Propofol reduces postoperative mental confusion compared with other induction agents.

Volatiles. MAC decreases linearly with age. Volatiles with rapid elimination, e.g. desflurane, may reduce postoperative mental confusion. Isoflurane, desflurane and sevoflurane have fewer cardiovascular side-effects than other volatiles.

Opioids (Table 6.2). Smaller V_D with higher initial plasma concentrations. Increased elimination half-life (↓ clearance greater than ↓ V_D). Decreased protein binding of pethidine with increasing age.

Table 6.2 Half-life of opioids

Muscle relaxants. Reduced plasma cholinesterase but minimal effect on hydrolysis. There are conflicting results for atracurium and vecuronium. Probably little change in initial dose requirements but prolonged elimination. No change in dose requirements or elimination of cisatracurium, but 30% increase in time to effective block. Pancuronium and gallamine cause tachycardia, worsening any myocardial ischaemia.

Anticholinergics. No change in dose but slower onset of action and prolonged muscarinic side-effects.

Local anaesthetics. Decreased elimination of lidocaine and bupivacaine with increased risk of toxicity.

Regional anaesthesia

In the elderly, regional anaesthesia decreases postoperative mental confusion and allows immediate recognition of angina, TIAs and mental confusion during TURP. Although some studies show benefits from regional anaesthesia, e.g. reduced incidence of MI, DVT, confusion, postoperative hypoxia, and decreased blood loss, others have reported increased risk of CVA and intraoperative hypotension. Meta-analysis shows trend towards reduced early mortality using regional anaesthesia.

Central anticholinergic syndrome

General principles of anaesthetic management

History

Epidemiology

The average number of reported suspected anaphylactic reactions related to anaesthesia is 55 p.a. compared with an average of 319 for all drugs. A total of 10% of anaesthetic reports were of fatalities, compared with 3.7% for all drugs reported. It is estimated, however, that there may be as many as 175–1000 severe reactions in the UK each year (1:5000–25 000 anaesthetics), with an overall mortality of 3.4%.

Some 90% occur within 10 min of drug administration. It is more common in females (5:1 neuromuscular blocking drugs; 3:1 thiopentone).

Types of allergic reaction

Hypersensitivity reactions

Mast cells

Found in perivascular tissue, gut mucosa, lung and skin. Up to 10% of their total weight is histamine. Stimulation causes release of histamine, eosinophil and neutrophil chemotactic factors, leukotrienes, prostaglandins, platelet-activating factor and kinins.

Hypersensitivity to drugs (Fig. 6.1)

In a French study (Laxenaire 2001), overall incidence of reactions was 1 in 13 000 anaesthetics, while the incidence of anaphylaxis to neuromuscular blocking agents was 1 in 6500 anaesthetics. Causes included neuromuscular blocking drugs (62%), latex (17%), antibiotics (8%), hypnotics (5%), colloids (3%) and opioids (3%).

Figure 6.1 Causes of life-threatening allergic reactions during anaesthesia.

(Data from Laxenaire 2001.)

Cross-reactivity may occur between drugs with similar structures, causing a type I hypersensitivity reaction to a drug to which the patient has not previously been exposed. In 70% of patients found to be allergic to a neuromuscular blocking drug, cross-reactivity was found to others; 17% of those allergic to a neuromuscular blocking drug had not had anaesthesia before.

Clinical symptoms (Fig. 6.2)

Awake patients may experience a metallic taste and a sense of impending doom. Commonest symptoms are hypotension (80%), rash/erythema (50%) and bronchospasm (36%). Tachycardia due to chronotropic effects of histamine and secondary release of adrenaline and noradrenaline. SVR is decreased by as much as 80% due to direct effect of histamine. Other symptoms include:

Figure 6.2 The first clinical feature of an anaphylactic reaction.

(Data from Whittington and Fisher 1998.)

CVS. Arrhythmias, pulmonary hypertension

Respiratory. Pharyngeal and laryngeal oedema (24%), rhinitis, pulmonary oedema

GI. Nausea and vomiting, diarrhoea, abdominal colic

Other. Generalized oedema (7%).

Factors which increase severity included asthma, β-blockade and neuraxial anaesthesia. All of these states are associated with reduced endogenous catecholamine response.

Treatment

Prophylaxis

Prophylaxis with antihistamines (H₁ and H₂) does not reduce the incidence of allergic reactions, but reduces mortality if they occur.

Screening

There is no method of predicting sensitivity to anaesthetic drugs. A history of previous exposure is not necessary for an anaphylactic reaction. The use of test doses of intravenous drugs is not an appropriate method of testing for anaphylaxis. Anaphylaxis has resulted from very small doses.

Anaesthesia for the atopic patient

There is some evidence that mast cells may degranulate more readily in atopic patients, but no evidence that atopic patients are any more susceptible to drug-mediated allergic reactions. Consider using drugs with low incidence of reaction, i.e. ketamine, etomidate and pancuronium.

Blood donors

Some 17 million units of blood are donated in Europe each year. Each unit is screened for antibodies to:

Blood groups

The ABO blood groups are summarized in Table 6.3.

Table 6.3 Summary of ABO blood groups

Coagulation cascade

Products

Whole blood

• 500 mL per bag with a haematocrit of 0.40

• No functioning platelets after 2–3 days; ↓ 2,3-DPG by 2 weeks

• Normal concentrations of albumin and clotting factors, except factors V and VIII, which are reduced to 10–20% of normal

• Not sterilized, so there is a risk of transmitted pathogens.

Red cell concentrate (packed cells): 2.2 × 10⁶ units used p.a. in the UK

• 250 mL per bag with haematocrit of 0.60

• No functioning platelets; 2,3-DPG levels maintained for 14 days

• Storage is 35 days with SAGM (saline, adenine, glucose, mannitol); 42 days with A-CPD (adenine, citrate, phosphate, dextrose).

Platelet concentrates: 260 000 units used p.a. in the UK

• Usually as a pool of 5–6 single unit donations; 4 units of platelets contain 1 unit FFP

• High incidence of transfusion-related acute lung injury (TRALI) associated with platelet transfusions. Usually due to an interaction between leucocyte antibodies in donor plasma and the corresponding antigen in the patient

• Infection risk. Increased by multiple donors and platelets >3 days old

• Use ABO-compatible platelets. Maximum storage is 5 days at 4°C.

Fresh frozen plasma (FFP): 300 000 units used p.a. in the UK

• Prepared from plasma from single donation; 150 mL per bag

• Contains all clotting factors, albumin and gammaglobulin

• Use within 24 h of thawing if kept at 4°C

• Must be ABO-compatible and Rh(D)-negative if recipient is a Rh(D) fertile female

• Risk of anaphylactic reactions.

Cryoprecipitate: 100 000 units used p.a. in the UK

• Precipitates from FFP when slowly thawed; supplied as 6–8 units

• High in factor VIII, fibrinogen and von Willebrand factor

• Indicated for DIC and von Willebrand’s disease.

Human albumin solution

Prepared by fractionation of multiple units of plasma giving 96% albumin and 4% globulin. Available as 4.5 or 20% (hyperoncotic) solution. Each 20 g of albumin requires 20 000 blood donations. Pasteurized at 60°C for 10 h to kill all microorganisms including viruses.

Factor VIII concentrate

• Freeze-dried protein as 250 units

• Sterilized to inactivate viruses.

Factor IX concentrate

• Freeze-dried protein as 250 units

• Sterilized to inactivate viruses

• Also contains factors II and X.

Immunoglobulin products

• Fractionation of plasma to produce pool with >90% IgG

• No risk of viral transmission

• Used for immune thrombocytopenia and immunodeficiency states.

Recombinant blood products

Recombinant FVIIa

rFVIIa initially developed to treat bleeding in haemophiliacs. FVIIa binds to tissue factor on damaged vascular beds to activate FIX and FX. The subsequent conversion of prothrombin to thrombin, activates platelets FVIII, FV and FXI and results in a large thrombin burst to transform fibrinogen to fibrin (Fig. 6.3). A recent meta-analysis of seven randomized clinical trials showed a reduction in blood transfusion requirements with no major safety concern (Ranucci 2008). Concerns remain regarding possible risks of thrombotic events.

Figure 6.3 Clotting cascade.

Transfusion reactions

Acute

• Haemolysis – due to antibodies directed against red cells

• Fever – donor leucocytes attack host red cells

• Anaphylaxis – due to antibodies directed against recipient IgA

• Transfusion-related acute lung injury – due to donor antibodies directed against leucocytes. Clinically identical to ARDS

• Hyperkalaemia – 5–10 mmol K⁺ in a unit of blood stored for 4–5 weeks. Effects of additional K⁺ are exacerbated by acidosis and hypothermia. Hyperkalaemia is usually transient

• Citrate toxicity – citrate is added as a preservative to bind excess calcium and prevent clotting. Metabolized to bicarbonate. Excess causes metabolic alkalosis

• Acid–base disturbance – citrate from preservative and lactate from red cells

• Hypocalcaemia – citrate anticoagulant binds ionized calcium; ↓ BP, ↓ pulse pressure. Give CaCl₂ only if there are symptoms/signs (not Ca²⁺ gluconate, which must be metabolized to release free Ca²⁺)

• Febrile reaction – due to bacterial contamination

• Microemboli – aggregates of all cellular components, increase with age of blood. Cause complement activation, haemolysis and thrombocytopenia. Removed by 170 μm filter; +/– 40 μm screen and depth filters

• Hypothermia – left shift of O₂ dissociation curve, platelet and clotting dysfunction

• Air embolus

• Fluid overload.

Delayed

• Haemolytic transfusion reaction – from red cell antibodies

• Graft-versus-host disease

• Alloimmunization (reaction to minor foreign antigens) – 10% of all transfusion reactions:

– red cell antibodies including anti-Rh(D)

– leucocyte antibodies

– platelet antibodies

• Viral infection – hepatitis B (<1:20 000 units) and C (<1:1 000 000 units), HIV (<1:4 000 000 units), cytomegalovirus, parvovirus (causes aplastic anaemia in sickle cell patients)

• Other infections – syphilis, malaria, trypanosomiasis

• Prions – risk of acquiring variant Creutzfeldt–Jakob disease (vCJD) is unknown. To minimize risk, UK National Blood Service leuco depletes blood, obtains plasma for fractionation from countries other than the UK and excludes donors who themselves received transfusions before 1980. At present, no test for vCJD exists.

• Tumour recurrence – increased risk

• Sensitization – resulting in antibody formation and subsequent difficulties with cross-matching

• Iron overload – occurs with repeated transfusions.

Massive blood transfusion

Defined as the acute administration of more than 1.5 times the patient’s blood volume, or replacement of the patient’s total blood volume within 24 h.

Blood groups for urgent transfusion are:

• Rh(D)-negative if patient not cross-matched

• Uncross-matched blood (type-specific) if patient’s blood group is known

Blood transfusions can be avoided by:

• reducing blood loss – hypotensive anaesthesia, antifibrinolytic agents

• tolerating a lower haematocrit

Guidelines for Autologous Blood Transfusion

British Committee for Standards in Haematology Blood Transfusion Task Force 1997

Summary

The purpose of all forms of autologous transfusion (acute preoperative haemodilution and preoperative donation or intraoperative cell salvage) is to avoid the transfusion of allogeneic blood and the associated risks. Autologous transfusion procedures are not usually acceptable to Jehovah’s Witnesses, although some accept intraoperative cell salvage.

Intraoperative cell salvage

Indications. Elective and emergency surgery with expected blood loss >20% total body volume.

Contraindications. Bacterial contamination of wound, malignant disease and sickle cell disease.

Acute preoperative haemodilution and preoperative donation

Indications. Elective surgery with expected blood loss >20% total body volume.

Contraindications. Aortic stenosis, unstable angina, and moderate to severe left ventricular impairment (Napier et al, 1997).

Blood Transfusion and the Anaesthetist – Red Cell Transfusion

Association of Anaesthetists of Great Britain and Ireland, June 2008

Summary

1. The decision to transfuse should always be made on an individual patient basis.

2. Patients need not be transfused to achieve a ‘normal’ haemoglobin concentration.

3. Anaesthetists should play a lead role in good preoperative assessment and preparation.

4. Departmental guidelines should be drawn up on matters of blood transfusion and be readily available for reference.

5. A permanent record of the administration of each unit of red blood cells is required by European law.

6. Record the reason for preoperative and postoperative transfusions in the clinical notes.

7. Local surgical blood ordering schedules, once developed, need to be reviewed at regular intervals by auditing red cell use.

8. Every Hospital Transfusion Committee is advised to include a representative from the Department of Anaesthesia.

Blood Transfusion and the Anaesthetist – Blood Component Therapy

Association of Anaesthetists of Great Britain and Ireland, December 2005

Recommendations

• Assessment of haemostasis in the preoperative period can reduce perioperative blood loss.

• Red cell concentrates do not contain coagulation factors or platelets, so the use of blood components (fresh frozen plasma (FFP) and platelets) needs to be considered early in managing a patient with massive haemorrhage.

• Emergency use of blood components requires assessment of haemostasis in advance of administration even if empirical use is necessary.

• The use of near-patient testing devices can improve decision making on the use of blood components.

• Thawed FFP can be stored at 4°C and can be used safely within 24 h.

• Thawed FFP kept at room temperature must be infused within 4 h.

• Vitamin K ± prothrombin complex concentrate (PCC) is recommended to reverse warfarin. FFP is indicated when there is severe bleeding or when PCC is unavailable.

• Platelet transfusion in the bleeding patient, or a patient requiring urgent surgery, is indicated at a platelet count <50 × 10⁹.L^-1 but in stable non-bleeding patients in intensive care, a trigger of 10 × 10⁹.L^-1 is acceptable.

• Component therapy should not be used to make regional anaesthesia possible if there are alternative anaesthetic methods available.

Blood Transfusion and the Anaesthetist – Intraoperative Cell Salvage

Association of Anaesthetists of Great Britain and Ireland, September 2009

Recommendations

• The use of intraoperative cell salvage (ICS) reduces the demand on allogeneic (donor) red cells and is a cost-effective measure.

• Trusts should provide the resources required to set up and maintain an ICS service in a safe and appropriate manner.

• Each Trust needs to ensure there is a clinical lead for ICS.

• A member of the theatre management team is responsible for ensuring overall management and facilitation of the ICS service.

• All personnel using ICS must be adequately trained and competent in its use.

• Preoperative assessment clinics should provide information on ICS to patients.

• All ICS cases undertaken require documentation and audit of use to enable future service planning and quality assurance.

Operative indications

• Anticipated blood loss >1000 mL or >20% estimated blood volume.

• Patients with a low HB or increased risk factors for bleeding.

• Patients with multiple antibodies or rare blood types.

• Patients with objections to receiving allogeneic (donor) blood.

Substances that should not be aspirated in the ICS system

• Antibiotics not licensed for i.v. use

• Iodine

• Topical clotting agents

• Orthopaedic cement.

Special circumstances

Malignancy – Concerns regarding reinfusion of malignant cells. Recent studies of the use if ICS during surgery for hepatocellular and bladder/prostate cancer have shown no difference in recurrence rates or long-term survival in patients receiving ICS; conversely, there is good evidence that allogeneic blood transfusion is an independent factor for postoperative infection and disease recurrence. The use of ICS in urological malignancies was approved by NICE in 2008.

Obstetrics – No proven cases of amniotic fluid embolus caused by reinfusion of salvaged blood. The use of ICS in obstetrics was approved by NICE in 2005.

Bowel contamination – Concern regarding infection risk if contaminated blood (with microorganisms) is reinfused. A RCT of ICS in abdominal trauma showed no increased infection risk when using ICS. Some case reports have suggested that reinfused blood in these patients may cause hypotension.

• transfusing autologous blood – prior donation, use of cell saver

• artificial blood

• erythropoietin.

Antifibrinolytic agents

Antifibrinolytic agents, e.g. tranexamic acid (aprotinin was withdrawn because of concerns about excess mortality and renal failure), bind to plasminogen and plasmin to interfere with their ability to split fibrinogen. Prostatic plasminogen activator is released during prostate surgery to cause bleeding, inactivated by antifibrinolytic agents. Antifibrinolytic agents may reduce bleeding in cardiac surgery following cardiopulmonary bypass.

Artificial blood (Fig. 6.4)

Perfluorocarbons. Inert carbon chains with oxygen solubility 20 times that of plasma. One study showing that perfluorocarbon emulsion may limit transfusion requirements, but trend towards greater morbidity and mortality (Spahn et al 2005).

Figure 6.4 Oxygen dissociation curve for oxygen-carrying molecules.

Recombinant Hb (rHb1.1). Modified human haemoglobin tetramer cross-linked with a glycine bridge between the alpha subunits. Produced from E. coli or yeast. Cross-linking prevents renal excretion. Cleared by the reticuloendothelial system within 24 h.

Purified Hb. From expired red cells, e.g. diaspirin cross-linked haemoglobin. Now abandoned because of higher mortality in some trauma studies.

Jehovah’s Witnesses

For the life of the flesh is in the blood: and I have given it to you upon the altar to make atonement for your souls: for it is the blood that maketh an atonement for the soul. Therefore I said unto the children of Israel, No soul of you shall eat blood, neither shall any stranger that sojourneth among you eat blood.

(Leviticus 17: 10–12; see also Genesis 9: 3–4 and Acts 15: 28–29).

There are an estimated 145 000 Jehovah’s Witnesses in the UK. They refuse administration of all blood and usually all blood products. They will allow blood to be retransfused if it has not lost contact with the circulation, e.g. cardiopulmonary bypass. The Children and Young Persons Act 1933 states that parents have a duty of care to their children which is not fulfilled if permission for a life-saving blood transfusion is withheld. Doctors can apply to the courts for permission to give blood against the parents’ wishes, but in an emergency, blood can be given to children without consulting the courts. Children under the age of 16 can consent to a blood transfusion if they understand the issues involved, but may not refuse blood.

Clinical issues

Anaesthetists have the right to refuse to anaesthetize an elective case (when referral can be made to other colleagues) but must anaesthetize an emergency case if failure to do so would harm the patient. Ideally, consultant staff should be involved with patient care.

Preoperative assessment should take place as early as possible. Anaemia should be treated. Use of iron supplements and erythropoietin should be considered. Patients must be seen alone to avoid undue influence from other family/church members. The patient must be made fully aware of the risks of refusal of blood products. It must be clarified which blood products and techniques (e.g. cell saver) are acceptable.

Intraoperative management

Blood loss >500 mL in adults is associated with increased mortality. Techniques to minimize blood loss include positioning to avoid venous congestion, hypotensive anaesthesia, use of tourniquets, meticulous haemostasis, use of vasoconstrictors, acute hypervolaemic haemodilution and use of a cell saver. Antifibrinolytics (e.g. tranexamic acid) may also reduce blood loss. Recombinant factor VIIa has been used successfully in these patients.

Postoperative care

• Early detection and correction of postoperative oozing

• Consider elective ventilation to increase oxygen delivery

• Active cooling reduces oxygen demand and increases dissolved oxygen carriage

• Hyperbaric oxygen therapy may also be of benefit.

Management of Anaesthesia for Jehovah’s Witnesses

Association of Anaesthetists of Great Britain and Ireland 2005 (2E)

Recommendations

1. Wherever possible, consultant staff (anaesthetists and surgeons) should be directly involved throughout the care of Jehovah’s Witness patients.

2. Departments of anaesthesia should review their procedure for being alerted at an early stage of the scheduling of Jehovah’s Witness patients for elective surgery.

3. Departments should keep a regularly updated list of those senior members prepared to care for followers of the Jehovah’s Witness faith.

4. In an emergency, an anaesthetist is obliged to care for a patient in accordance with the patient’s wishes.

5. Properly executed Advance Directives must be respected and special Jehovah’s Witness consent forms should be widely available for use as required.

6. All Jehovah’s Witnesses must be consulted individually, whenever possible, to ascertain what treatments they will accept.

7. Discussions with individual Jehovah’s Witness patients should be fully documented and their acceptance or rejection of treatments recorded and witnessed.

8. In the case of children, local procedures for application to the High Court for a ‘Specific Issue Order’ should be reviewed and available for reference.

9. A ‘Specific Issue Order’ or equivalent should only be applied for when it is felt to be entirely necessary to save the child in an elective or semi-elective situation.

10. In a life-threatening emergency in a child unable to give competent consent, all life-saving treatment should be given, irrespective of the parents’ wishes.

Consumptive coagulopathies

Disseminated intravascular coagulation (DIC)

Consumptive coagulopathy associated with activation of both coagulation and fibrinolytic pathways. Commonest causes are sepsis, obstetric-related conditions or shock. Treatment should be guided by clinical signs and coagulation results, to include platelet concentrate, fresh frozen plasma, cryoprecipitate (a source of fibrinogen) and red cells. Antifibrinolytic agents may risk permanent clot formation. Use of heparin is controversial, but may be of benefit in amniotic fluid embolism.

Thromboelastography

Thromboelastography (TEG) was first described in 1948, but the risks of blood product transfusion and financial costs have led to a renewed interest in improving coagulation management.

Principles of TEG

TEG uses the viscoelastic changes of blood that are associated with fibrin polymerization. Clot formation is induced by putting whole blood in a low shear environment (which mimics sluggish venous flow). The patterns of shear-elasticity alteration reveal the kinetics of clot formation and growth, and the strength and stability of the formed clot. The kinetics of clot formation reflects the adequacy of quantitative factors available, while the clot strength/stability reveals the ability of the clot to perform the work of haemostasis.

The thrombelastograph consists of a larger vertical cylinder within which sits a smaller cylinder. The outer cylinder (cuvette) of the thrombelastograph oscillates at a fixed frequency. The internal cylinder (pin) of the thrombelastograph is free to move. As the blood sample placed between the cylinders clots, it forms a mechanical bond between the inner and outer cylinders of the thrombelastograph such that the oscillatory motion of the outer cylinder is transmitted to the inner cylinder. The stronger the clot, the greater the adhesion between the two cylinders and the larger the transmitted oscillation of the inner cylinder. The oscillations of the smaller cylinder are amplified to create a TEG trace.

TEG endpoints (Fig. 6.5)

R time

The time from the start of measurement until the start of clot formation. Reflects the initiation of clotting, thrombin formation, and the start of fibrin polymerization.

Figure 6.5 A thromboelastograph tracing, showing the endpoints used for TEG analysis.

Prolonged R time is caused by:

• Factor deficiency

• Heparin

• Severe thrombocytopenia

• Severe hypofibrinogenaemia.

Short R time is caused by:

• Hypercoagulable states.

K time

The time from starting clot formation until amplitude of 20 mm is reached. Represents fibrin polymerization, stabilization of the clot with platelets and FXIII.

Prolonged by:

• Factor deficiency

• Thrombocytopaenia

• Thrombocytopathy

• Hypofibrinogenaemia.

Shortened by:

• Hypercoagulable state.

Angle (α)

Measures the rapidity of fibrin build-up and cross-linking (clot strengthening).

Increased angle is caused by:

• Hypercoagulable state.

Decreased α is caused by:

• Hypofibrinogenaemia

• Thrombocytopaenia.

Maximum amplitude (MA)

A direct function of fibrin and platelet bonding via GPIIb/IIIa, reflecting ultimate clot strength. Correlates with platelet numbers and function, and fibrinogen levels.

Increased by:

• Hypercoagulable state.

Decreased by:

• Thrombocytopaenia

• Thrombocytopathy

• Hypofibrinogenaemia.

LY30 or LY60

Measures percentage decrease in amplitude at 30 or 60 min post-MA, indicating the degree of fibrinolysis. (Normal range <7.5%.)

This TEG trace is charted over time, producing a distinct shape according to the coagulation profile (Fig. 6.6).

Figure 6.6 Common patterns of abnormal TEG profiles.

Advantages of TEG

• Provides initial results within 10–20 min

• Good at differentiating between surgical and coagulopathic bleeding (negative predictive value >90%)

• Has been shown to reduce transfusion requirements.

Limitations of TEG

• Poor at detecting platelet dysfunction (TEG uses celite or kaolin activation of the clotting cascade. This results in supra-physiological thrombin generation, which is sufficient to activate even platelets inhibited by aspirin or clopidogrel)

• Whole blood TEGs are performed at 37°C, masking any anticoagulant effects of hypothermia.

Epidemiology

There are 10 000 burns admissions p.a. in the UK, of which 600 are fatal; 35% of burn injuries occur in children. Most burns are scalds (children), flame burns and flash burns (adults); also electrical and chemical burns. Cold injury (frostbite) is rare in the UK.

Treatment of burn injury

Airway

Direct thermal injury, toxic gases and smoke inhalation cause:

• upper airway oedema and obstruction

• lung parenchymal damage

• carbon monoxide poisoning

• cyanide poisoning (burning plastic).

Breathing

Monitor respiratory function, especially if there is inhalational injury. Indicators of an upper airway burn include voice changes, CXR changes, carboxyhaemoglobinaemia >15%, or compromised arterial blood gases.

Humidify inspired gases if there is upper airway burn. Intubate immediately if severe airway burn, since facial oedema will develop rapidly over the initial 24 h following a facial burn and may make intubation very difficult.

Carbon monoxide poisoning. 1000 deaths p.a. in the UK. The symptoms of CO poisoning are given in Table 6.4. HbCO results in over reading of the pulse oximeter. The half-life of carbon monoxide (250 times the affinity of O₂ for Hb) is:

• room air – 5 h

• 100% O₂1 h.

Table 6.4 Symptoms of carbon monoxide poisoning

%HbCO	Symptoms
0–10	None
10–20	Headache, malaise
30–40	Nausea and vomiting, slowing of mental activity
>60–70	CVS collapse, death. Consider hyperbaric O2 therapy

Hyperbaric oxygen treatment is recommended with COHb >20%, loss of consciousness at any stage, neurological signs/symptoms arrhythmias, or pregnancy. Reduces the risk of serious neurological deficit and shortens recovery.

Cyanide poisoning. Causes metabolic acidosis, raised lactate, arterial hypoxaemia and increased anion gap. Consider treatment with cyanide-chelating agents (dicobalt edetate) or agents accelerating cyanide metabolism (sodium thiosulphate).

Circulation

Risk of profound hypovolaemia with hypotension. Early fluid shifts result in loss of fluid from the plasma into the extracellular tissue around the burn. This fluid is similar in composition to plasma with equal electrolyte content but with slightly less protein. If crystalloid is used for resuscitation, larger volumes are necessary and may result in tissue oedema. Fluid loss is maximal in the first few hours and returns to basal levels by 36 h.

Blood loss during surgical debridement may be rapid and exceed 2 mL/kg per 1% of burn desloughed.

Extent and depth of burn

Burn size. This is estimated using the ‘Rule of Nines’ (Fig. 6.7).

Figure 6.7 ‘Rule of Nines’ for assessing burn area.

Depth of burn

Superficial. Damage to epidermis. Erythema but no blistering. Painful. Heals in 2–3 days.

Partial thickness. Destruction of epidermis and dermis with formation of blisters. If deep, may also include islets of fat. Painful. Heals within 10 days as fresh epidermis grows out from hair follicles but deep partial thickness burns may be slow to heal.

Full thickness. Complete loss of epidermis and dermis down to subcutaneous fat. Loss of pain receptors renders burn painless. The burn is either white or charred with eschar. Heals by wound contraction and thus if circumferential may require escharotomies in the acute stage.

Fluid replacement. Formal fluid resuscitation is commenced in adults with >15% burns or in children with >10% burns. Ringer’s lactate is the crystalloid of choice. Hypertonic saline may reduce fluid volumes and oedema, but some studies have shown that it causes hypernatraemia, renal failure and increased mortality.

These regimens are given in addition to the normal daily fluid requirements (usually given as 5% dextrose or dextrose saline). Volumes may need increasing if clinical indicators show inadequate resuscitation (mental status, vital signs, urine output, capillary refill, CVP, etc.).

Check electrolytes, haematocrit and plasma and urine osmolality every 4 h. Low volume urine with osmolality >450 suggests continuing hypovolaemia. Transfuse blood if haematocrit <0.3.

Common fluid replacement formulae:

• Parkland (commonest in UK)

– 4 mL/kg crystalloid × % burn

– (½ given over first 8 h, ¼ over next 8 h, ¼ over next 8 h).

• Muir and Barclay (Mount Vernon formula)

– 0.5 mL/kg colloid (PPF/albumin) × % burn given over 4, 4, 4, 6 and 6 h.

• Brook

– 0.5 mL/kg colloid and 1.5 mL/kg crystalloid × % burn

– (½ given over first 8 h, ¼ over next 8 h, ¼ over next 8 h).

Infection

May worsen depth of burn, risks spreading to become a systemic infection and may destroy any skin grafts. Patients at high risk both from loss of protective skin barrier and from generalized immunosuppression.

Nurse in as clean an area as possible because of high risk of infection. Take measures to avoid cross-infection. Use topical antimicrobial prophylaxis with silver sulphadiazine cream (Flamazine).

Antibiotic cover is necessary to cover dressing changes. Systemic antibiotics should not be given routinely.

Hypothermia

Impaired homeostatic control and heat loss through burns result in rapid onset of hypothermia, accelerated by general anaesthesia and cold fluids. Keep room at 30°C to minimize energy requirements and ensure use of blood warmer and heated mattress.

Multiple anaesthetics

Are required for dressing changes and skin grafting. Monitoring (e.g. ECG dot placement) may be difficult with extensive burns. Venous access may have to be gained through burnt tissue or by a cutdown.

Nutrition and GI

Early feeding is vital because of high catabolic state. NG tube may be necessary for feeding and to prevent acute gastric dilatation. Gastric stasis is common, in which case a nasojejunal tube is necessary. Calculate amount of feed needed according to Sutherland or modified Curreri formula. Aim for a calorie:nitrogen ratio of 100:1. Give gastric stress ulcer prophylaxis. Monitor blood sugar closely.

Analgesia

Any burns less than full thickness require large doses of opioid analgesia.

Surgical management

Superficial burns usually heal spontaneously within 10 days and do not require surgery.

Partial-thickness burns require frequent debridement and may require grafting if unhealed by 3 weeks.

Full-thickness burns require early debridement and grafting. Although early debridement of a large area further traumatizes the patient and may result in loss of a large blood volume, a delay in debridement risks wound colonization and septic shock and prolongs the catabolic state following injury. If full-thickness burns are not grafted, they may never heal, or if they do they will result in contractures.

Advantages

Guedel classification

Described for spontaneous respiration with diethyl ether in 1937.

• Stage 3: Surgical anaesthesia – automatic respiration to respiratory paralysis:

– Plane 1: Regular, large-volume respiration

Central, pinpoint pupils. Cessation of eye movements

Eyelid reflex abolished

– Plane 2: Thoracic component of respiration decreased

Loss of corneal reflex

– Plane 3: Respiration becoming diaphragmatic. Small volume

Laryngeal reflexes depressed

Pupils normal

– Plane 4: Irregular diaphragmatic, small-volume respiration

Dilated pupils

Carinal reflex depressed.

ASA grading (1963)

Congenital syndromes

Haemoglobinopathies

Sickle cell disease

Autosomal dominant inheritance. Affects people of African, Mediterranean, Indian, Caribbean and Middle Eastern descent. Found in 10% of black people in the UK.

The condition is due to substitution of glutamine by valine on position 6 of the β-chain of haemoglobin A to form HbS. Causes polymerization of deoxygenated haemoglobin at low P_ao₂ with alteration of the discoid cell to a rigid sickle shape. These abnormal cells increase blood viscosity and sludge in the microvascular circulation. Infarcts cause symptoms and signs of the disease. Sickling is precipitated by dehydration, acidosis, fever and hypoxia.

The heterozygous form, HbAS (sickle trait), has normal life expectancy with haemoglobin >11 g/dL, no clinical symptoms or signs and sickling only if P_ao₂ <2.5 kPa. Hb does not fall below 11.0.

The homozygous form, HbSS, usually presents by 6 months when HbF is replaced by HbS. Deoxygenation of HbS results in polymerization to form insoluble globin polymers. Associated with chronic anaemia, painful sickle crises, pulmonary thromboembolism, pulmonary, renal and bone infarcts, gallstones, priapism, TIAs and strokes. Splenic sequestration results in splenomegaly in infants, but multiple infarcts cause autosplenectomy by adulthood. Parvovirus causes aplastic crises. Target cells on blood film. HbSS sickles at P_ao₂ <5.0 kPa.

Haemoglobin S may combine with other haemoglobins, e.g. HbC, to give HbSC or with β-thalassaemia haemoglobin.

Diagnosis. Sickledex test causes sickling when affected erythrocytes are exposed to sodium metabisulphite. Unlike electrophoresis, it does not distinguish between homozygous and heterozygous conditions.

Anaesthetic considerations. Consider exchange transfusion if HbA <40%, aiming to reduce HbS to <25%. Postoperative mortality is about 5%. Patients are not suitable for day-case surgery. Impaired renal concentrating ability.

Reduce risk of sickling by:

• keeping well oxygenated

• good analgesia

• avoiding tourniquets, which induce sickling

• keeping warm

• keeping well hydrated

• prophylactic antibiotics.

A Sickle Crisis?

A Report of the National Confidential Enquiry into Patient Outcome and Death 2008

Principal recommendations

• A multidisciplinary and multi-agency approach is needed in the ongoing pain management of patients with sickle cell disease – essentially this takes place outside hospitals for the majority of patients.

• Cause of death in sickle cell disease patients must be better evaluated, whether by clinicians reviewing the records and writing a death certificate.

• All staff should be aware that people with sickle cell disease are subject to the diseases that other patients suffer from as well. If there is uncertainty as to whether the problem is sickle cell related, advice should be sought from an experienced clinician.

• All sickle cell disease patients should have a carefully maintained fluid balance chart for the duration of their admission.

• Patients with sickle cell disease or beta thalassaemia major should be managed by, or have access to, clinicians with experience of haemoglobinopathy management.

• Healthcare centres responsible for the management of patients with haemoglobinopathies should have access to protocols/guidelines from their regional specialist centre.

Porphyria

Autosomal dominant metabolic disorder of porphyrin synthesis. Porphyrins are tetrapyrrole rings involved in the synthesis of haemoglobin, myoglobin and cytochromes. There are two types of porphyria:

• erythropoietic – anaemia and liver disease only

• hepatic – potentially fatal.

Increased production of aminolaevulinic acid (ALA) and porphobilinogen (PBG), together with their reduced metabolism by porphobilinogen deaminase, causes symptoms:

Acute intermittent porphyria (hepatic) is the commonest form, presenting as hypertension (36%), tachycardia (80%) and abdominal pain (95%) due to autonomic neuropathy; also peripheral neuropathy (30%), bulbar palsy (30%), convulsions (20%) and mental confusion (55%). Urine turns red after standing in sunlight. Underlying defect is decreased activity of porphobilinogen deaminase.

Acute episodes are precipitated by:

• infection, starvation and dehydration

• steroids, barbiturates, etomidate

• alcohol

• oral contraceptive pill

• cimetidine, erythromycin, sulphonamides

• prochlorperazine, metoclopramide.

Safe drugs

• Volatile agents and nitrous oxide

• Propofol, midazolam, diazepam

• Morphine, codeine, alfentanil, fentanyl

• Lidocaine, bupivacaine

• All muscle relaxants, including suxamethonium

• Anticholinergics, anticholinesterases.

Treatment. Identify and remove the cause if possible. Ensure adequate hydration and correct any electrolyte imbalance. Hypertension and tachycardia respond well to β-blockers. Treat generalized convulsions with diazepam. Ensure adequate analgesia with opioids. Specific treatment involves infusion of heme arginate, which directly increases negative feedback to ALA synthetase.

General anaesthesia. Best avoided, by using regional techniques, but document any peripheral neuropathy first. Total dose of drug administered and duration of anaesthetic influences the probability of triggering a porphyric crisis. Postoperatively, good analgesia avoids the stress of pain triggering an acute attack. Monitor postoperatively for 5 days since onset may be delayed.

Ankylosing spondylitis

An inflammatory condition of unknown aetiology, characterized by high ESR, fever, weight loss and anaemia. Causes progressive fibrosis, ossification and ankylosis of sacroiliac joints and spine. 50% have extra-articular involvement.

Difficult intubation may occur as a result of limited cervical spine movement and ankylosis of temporomandibular joint, limiting mouth opening in >10% patients. Cricoarytenoid arthritis presents as dyspnoea and hoarseness. Cardiovascular complications include aortic incompetence, mitral valve disease and conduction defects. Thoracic spine involvement limits chest expansion and is associated with pulmonary fibrosis.

Meyer–Overton theory

States that MAC × solubility = K (Fig. 6.8).

Figure 6.8 Meyer–Overton theory.

May provide some evidence that the site of action of the volatile agents is at a hydrophobic site, i.e. lipids within the cell membrane. However, many discrepancies have led to a move away from this theory.

Hydrate hypothesis (Pauling and Miller 1961)

The fact that the brain consists of 78% water led to the suggestion that anaesthetics act on hydrophobic molecules. However, there is poor correlation between anaesthetic potency and water solubility. This theory also predicted that two anaesthetic agents would have a synergistic effect, but volatile agents appear only to have an additive effect (Fig. 6.9).

Figure 6.9 Hydrate hypothesis.

Diagnosis of brainstem death

Management of patients for organ donation

Guidelines for the Management of Potential Organ and Tissue Donors

Department of Health 1998

It is important to maintain normal physiological parameters to prevent end-organ damage. As many as 20% of hearts from otherwise suitable patients are lost to donation through poor management. Sympathetic storm may occur as ICP rises, causing brainstem ischaemia (tachycardia, hypertension, neurogenic pulmonary oedema), which if untreated will cause end organ damage. As vasomotor centres in the brainstem die, endogenous sympathetic activity is lost and the patient develops a relative vasodilatory hypovolaemia and hypotension. Brainstem death also results in endocrine failure (diabetes insipidus, cortisol deficiency, hypothyroidism) and impaired thermoregulation.

Management of recipients for renal transplantation

(See also ‘Anaesthesia and renal failure’ section in Ch. 4.)

Management of recipients for cardiac/lung transplantation

Survival rates are improving as follows:

Similar anaesthetic technique to that for cardiac surgery.

Specific problems with management include:

Post-Anaesthetic Recovery

Physiology

The vomiting centre is situated in the reticular formation of the medulla within the blood–brain barrier. The chemoreceptor trigger zone is situated in the area postrema on the floor of the IV ventricle and receives input from many afferents (Fig. 6.11).

Figure 6.11 Afferent pathways of the vomiting reflex.

Effects of PONV

Risk factors for PONV

Surgery associated with PONV

Perioperative drugs causing PONV

Prevention

Treatment

Use antiemetic prophylaxis in high-risk patients. (Low-dose droperidol 0.005 mg/kg may be more effective than high dose.)

Use drug appropriate to neurotransmitter: anticholinergic for vagally mediated vomiting, e.g. hyoscine; antidopaminergic for opioid-mediated vomiting, e.g. phenothiazines, butyrophenones. Ondansetron (5HT₃ antagonist) may be useful in chemotherapy-induced vomiting and vomiting resistant to conventional drugs where it is more effective than metoclopramide or droperidol.

Investigations

Blanket routine preoperative investigations are inefficient, expensive and unnecessary. Medical and anaesthetic problems are identified more efficiently by the taking of a history and by the physical examination of patients. No investigations are required prior to minor surgery in otherwise healthy patients.

Adult basic life support guidelines

Basic life support is summarized in Figure 6.12a. The 2005 guidelines revised the compression:ventilation ratio to 30:2 following evidence that even short interruptions to external chest compression are disastrous for outcome. Compression-only CPR is acceptable if the rescuer is unwilling or unable to perform mouth-to-mouth ventilation.

Figure 6.12 (A) Adult basic life support guidelines. (Resuscitation Council (UK) 2010 © RC(UK).)

(B) Adult advanced life support guidelines. (Resuscitation Council (UK) 2010 © RC(UK).)

Adult advanced life support guidelines (Fig. 6.12b)

Defibrillation

Biphasic waveforms (Fig. 6.13) have the following advantages over older monophasic waveforms (Fig. 6.14):

• Lower energy benefits – greater first shock efficacy at lower energy levels

• Biphasic defibrillators can alter the waveform to compensate for variations in transthoracic impedance.

• Less post-shock dysfunction – 90% less post-shock ST segment changes and fewer post-shock arrhythmias.

Figure 6.13 Biphasic waveform (biphasic truncated exponential).

Figure 6.14 Monophasic waveform (damped sinusoidal).

One paddle/pad should be placed below the right clavicle in the midclavicular line and the other over the lower left ribs in the mid/anterior axillary line (just outside the position of the normal cardiac apex).

Defibrillation strategy

Treat VF/pulseless VT with a single shock, followed by immediate resumption of CPR. Do not reassess the rhythm or feel for a pulse. After 2 min of CPR, check the rhythm and give another shock (if indicated). If VF/pulseless VT occurs in the cardiac catheterisation laboratory or in the immediate post-operative period following cardiac surgery give up to three quick successive (stacked) shocks.

The initial shock energy level for biphasic defibrillators is 150–200 J. Give second and subsequent shocks at the same or higher levels. The shock energy level when using a monophasic defibrillator is 360 J for both the initial and subsequent shocks.

Drugs

Delivery of drugs via a tracheal tube is no longer recommended – if intravenous (IV) access cannot be achieved, give drugs by the intraosseous (IO) route. Drugs administered via peripheral veins or IO should be flushed with 20 ml of 0.9% saline.

Adrenaline (epinephrine)

The α-adrenergic effects of adrenaline cause vasoconstriction, which increases myocardial and cerebral perfusion pressure during cardiac arrest; however, there is no placebo-controlled study that shows that the routine use of any vasopressor at any stage during human cardiac arrest increases survival to hospital discharge. Despite the lack of human data the use of adrenaline is still recommended, based largely on experimental data.

When treating VF/VT cardiac arrest, adrenaline 1 mg is given once chest compressions have restarted after the third shock and then every 3–5 minutes (during alternate cycles of CPR). In the 2005 Guidelines, adrenaline was given just before third shock. This subtle change in the timing of adrenaline administration is to enable drug delivery to be separated totally from attempted defibrillation. In this way, it is hoped that shock delivery will be more efficient and will minimise the interruption in chest compressions. In patients in asystole or PEA, give adrenaline 1 mg IV immediately once IV/IO access is achieved.

Atropine

Atropine is no longer recommended for routine use in asystole or pulseless electrical activity.

Amiodarone

The use of amiodarone in shock-refractory VF improves survival to hospital admission compared with lidocaine. If VF/VT persists after three shocks, give amiodarone 300 mg by bolus injection after the third shock. A further dose of 150 mg may be given for recurrent or refractory VF/VT, followed by an infusion of 900 mg over 24 h. Lidocaine 1 mg.kg^-1 may be used as an alternative if amiodarone is not available.

Bicarbonate

Although acidosis is known to depress myocardial contractility (pH <7.2), reduce tissue oxygen delivery and increase susceptibility to VF, there is no good evidence that correction of pH improves outcome of CPR.

Side-effects of bicarbonate include:

• increased osmolality through large sodium load

• increased P_aco₂ causing respiratory acidosis

• metabolic alkalosis

• paradoxical intracellular acidosis (limited evidence)

• decreased ionized Ca²⁺

• impaired arterial oxygenation and reduced myocardial oxygen consumption

• increased risk of neonatal intraventricular haemorrhage.

Giving sodium bicarbonate routinely during cardiac arrest is not recommended. Give sodium bicarbonate (50 mmol) if cardiac arrest is associated with hyperkalaemia or tricyclic antidepressant overdose. Repeat the dose according to the clinical condition of the patient and the results of repeated blood gas analysis.

Magnesium

Give magnesium sulphate 8 mmol for refractory VF if there is any suspicion of hypomagnesaemia (e.g. patients on potassium-losing diuretics) or:

• ventricular tachyarrhythmias in the presence of possible hypomagnesaemia

• torsade de pointes

• digoxin toxicity.

Thrombolytics

The commonest cause of thromboembolic or mechanical circulatory obstruction is massive pulmonary embolus. If cardiac arrest is thought to be caused by pulmonary embolism, consider giving a thrombolytic drug immediately but be prepared to continue CPR for up to 90 min. Thrombolytics have been shown to be ineffective when given for cardiac arrest resulting from acute coronary artery thrombosis.

Post-resuscitation Care

A comprehensive, structured post-resuscitation treatment protocol may improve survival in cardiac arrest victims after ROSC. In particular:

• Unconscious adult patients with spontaneous circulation after out-of hospital (all rhythms) cardiac arrest should be cooled to 32–34°C for 12–24 h. Mild hypothermia may also benefit unconscious patients with spontaneous circulation after cardiac arrest in hospital.

• Hyperoxaemia after ROSC is achieved may cause harm. Therefore titrate inspired O₂ to achieve a SaO₂ of 94–98%.

• Blood glucose values >10 mmol.l^-1 should be treated, but hypoglycaemia must be avoided.

Resuscitation during pregnancy

• <25 weeks: as above

• 25–32 weeks: use wedge to relieve aortocaval compression

• >32 weeks: degree of aortocaval compression precludes effective CPR; therefore, perform immediate caesarean section whilst CPR is continued.

Guidelines for paediatric basic and advanced life support (Fig. 6.15a and b)

Causes of paediatric arrest are significantly different from those in adults. Cardiac arrest at birth is usually due to asphyxia; in infancy to respiratory illness or sepsis; and in later childhood to trauma.

Figure 6.15 (A) Paediatric basic life support guidelines. (Resuscitation Council (UK) 2010 © RC(UK).)

(B) Paediatric advanced life support guidelines. (Resuscitation Council (UK) 2010 © RC(UK).)

Trained responders should give 15 compressions: 2 ventilations. (Lay people should use the 30:2 compression:ventilation ratio). Massage at the junction of middle/lower third sternum and compress the chest to a depth of at least 1/3 the AP diameter at a rate of 100–120 per minute.

Humidified oxygen with as high a F_io₂ as possible should be used. (Once spontaneous circulation has been restored, O₂ should be titrated to limit the risk of hyperoxaemia.) Bag-mask ventilation is the preferred method for achieving airway control and ventilation. If this fails, a supraglottic airway device is an acceptable alternative. Once the airway is secured give 10 breaths/min.

Asystole is the commonest paediatric arrest arrhythmia and is usually preceded by an agonal bradycardia. VF occurs in only 6–9% of arrests, when shocks (all waveforms) should be given at 4 J.kg^-1. A standard AED can be used in children over 8 years. Purpose-made paediatric pads, or programmes which attenuate the energy output of an AED, are recommended for children between 1 and 8 years given after the third shock for shockable rhythms. The dose is repeated after the fifth shock, if still in VF/pulseless VT. Look for specific causes of VF, including congenital heart disease, hypothermia, tricyclic antidepressants and hyperkalaemia.

The initial dose of adrenaline is 10 μg.kg^-1. High-dose (100 μg.kg^-1) adrenaline may be considered for children where vasodilation may be significant, e.g. septic shock. Adrenaline is given after the third shock for shockable rhythms and then during every alternate cycle (i.e. every 3–5 minutes during CPR). Adrenaline is still initially given as soon as vascular access is available in the non-shockable side of the algorithm.

Hypernatraemia secondary to sodium bicarbonate administration greatly increases the risk of intracranial haemorrhage in neonates. The initial dose is 1 mmol.kg^-1 given as a slow bolus before the second dose of adrenaline. Give further doses of bicarbonate according to arterial or mixed venous pH. Calcium (chloride or gluconate) should be given in a dose of 10–30 mg.kg^-1.

Hypoglycaemia is common in sick infants. Check glucose during resuscitation and treat hypoglycaemia with glucose 0.5 g.kg^-1 as a 10% or 25% solution.

The commonest causes of electromechanical dissociation are hypovolaemia, cardiac tamponade and tension pneumothorax. Correct hypovolaemia with boluses of 20 mL.kg^-1 crystalloid or colloid.

If venous access cannot be gained within 90 s, use an intraosseous needle which is suitable for all resuscitation drugs, colloid, crystalloid and blood. It also allows samples of marrow aspirate to be withdrawn for estimation of haemoglobin, venous pH and electrolytes.

Apgar scores

Table 6.5 Apgar scores

Paediatric Resuscitation Drug Doses

• Adrenaline 10 μg.kg^-1. Consider 100 μg.kg^-1 in septic shock

• Atropine 20 μg.kg^-1

• Sodium bicarbonate 1–2 mmol.kg^-1. Further doses should be titrated against blood gases

• Calcium chloride 0.2 mL kg^-1 of the 10% solution

• Amiodarone 5 mg.kg^-1

• Glucose 0.5 g.kg^-1

• Furosemide 1 mg.kg^-1

• Crystalloid 20 mL.kg^-1 if hypovolaemic. Repeat three times and then give 10 mL.kg^-1 blood if shock persists.

Guidelines for the management of peri-arrest arrhythmias (Fig. 6.16a,b)

The 2010 European Resuscitation Council guidelines cover the management of bradyarrhythmias, broad complex tachycardias and narrow complex tachycardias (supraventricular tachycardias, SVTs), including atrial fibrillation.

Figure 6.16 (A) Adult bradycardia algorithm. (Resuscitation Council (UK) 2010 © RC(UK).)

(B) Adult tachycardia algorithm.

(Resuscitation Council (UK) 2010 © RC(UK).)

Physiology of circulation during closed chest massage

There are two theories of blood flow:

• Cardiac pump theory. Blood is ejected from the heart as it is squeezed between the sternum and spine. The aortic valve prevents retrograde flow.

• Thoracic pump theory. Cardiac massage raises intrathoracic pressure and forces blood out of the thorax. Venous valves and venous compression prevent retrograde flow.

Both mechanisms are probably involved. Adrenaline constricts vascular beds to direct most flow to the brain and heart, so although total cardiac output is 10–30%, brain and heart flows approach 50% of normal. All flows decrease rapidly with time.

Use of end-tidal CO₂ monitoring

CO₂ excretion during CPR is dependent upon cardiac output and not ventilation. A high correlation exists between P_ETco₂ and cardiac output, coronary perfusion pressure and survival from cardiac arrest. P_ETco₂ <10 mmHg during resuscitation is associated with an unsuccessful outcome. Monitoring P_ETco₂ during cardiac massage therefore provides feedback to optimize chest compression and may also give an early indication of operator fatigue. Current resuscitation guidelines encourage the use of end-tidal CO₂ monitoring both as a means of monitoring the effectiveness of CPR and for confirmation of correct tracheal tube placement.

Normal (Gaussian) distribution

A sample of data may form a normal distribution curve which is bell-shaped and symmetrical about the mean value, e.g. height, weight, heart rate (Fig. 6.17).Mean, median and mode

Figure 6.17 Normal (Gaussian) distribution curve. μ = mean; σ = standard deviation.

The mean, median and mode have identical values within normally distributed data (Fig. 6.18a).

Figure 6.18 Mean, median and mode: (A) normal distribution; (B) positively skewed distribution; (C) negatively skewed distribution.

Curves of normal distribution have symmetry about the mean. A curve that is not symmetrical is referred to as skewed. A curve is positively skewed if most data lie below the mean, and negatively skewed if most data lie above the mean. In a skewed distribution, mean, median and mode are not equal (Fig. 6.18b,c). The amount of skewness is given by the following equation:

where:

x = observed mean

= expected mean

n = number of observations

n – 1 = degrees of freedom (N).

A result of zero indicates a completely symmetrical distribution; positive values indicate positively skewed distribution and vice versa. Strongly skewed data must be examined using non-parametric tests.

Statistical tests (Tables 6.6, 6.7)

Linear correlation and linear regression

Observation of a scattergram may suggest some form of correlation between two variables (Fig. 6.19).

Figure 6.19 Scattergram of x against y.

The best-fit straight line is calculated for the data (Fig. 6.20). The position of the best-fit straight line is adjusted to minimize the sum of the distances d1–d4 so that Σd is a minimum.

Figure 6.20 Linear regression for scattergram data.

The best-fit line is given by the equation:

where:

x = independent variable

y = dependent variable

m = slope of the straight line

C = a constant.

Multiple linear regression is designed to establish any relationships when several variables are present within the same set of data.

Correlation coefficient

The correlation coefficient, r, is an indication of how close the points lie to the best-fit line. As the data lie closer to the best-fit line, r tends towards 1.0 (Fig. 6.21).

Figure 6.21 Correlation coefficients.

Bland–Altman plot

When comparing unrelated data, e.g. height versus weight, correlation coefficient is appropriate. When comparing related data (e.g. different methods of measuring the same variable), a Bland–Altman plot is more appropriate. The mean of each individual data pair is shown on the x-axis and the difference between each data pair on the y-axis. An example is given in Figure 6.22.

Figure 6.22 Bland–Altman plot.

Advanced Trauma Life Support

Primary survey

Secondary survey

Involves a systematic head-to-toe survey:

Fluids in resuscitation

Type of fluid

The recently completed safe versus albumin fluid evaluation (SAFE) trial in Australia showed no difference in outcomes among ICU patients receiving crystalloid vs colloid (albumin) as their primary resuscitative fluid.

Hypertonic saline is effective in restoring blood volume through hypertonic recruitment of interstitial and intracellular fluid. Although small clinical studies and animal studies have shown benefit, recent meta-analysis has failed to demonstrate any improvement in morbidity or mortality.

Head Injury: Triage, Assessment, Investigation and Early Management of Head Injury in Infants, Children and Adults

National Institute for Health and Clinical Excellence, September 2007

Investigation for injuries to the cervical spine

Which investigation?

• In most circumstances, plain radiographs are the initial investigation of choice to detect cervical spine injuries – three views of sufficient quality for reliable interpretation (two views for children under 10 years of age).

• CT imaging is recommended in some circumstances.

Figure 6.24 Assessment in emergency department.

(National Institute of Health and Clinical Excellence.)

• CT imaging is recommended in some circumstances.

• Children under 10 have increased risk from irradiation, so restrict CT imaging of cervical spine to children with indicators of more serious injury, in circumstances such as:

– severe head injury (GCS ≤8)

– strong suspicion of injury despite normal plain films

– plain films are inadequate.

As a minimum, CT imaging should cover any areas of concern or uncertainty on plain film or clinical grounds.

Figure 6.25 Selection of adults for CT scanning of the head. (National Institute of Health and Clinical Excellence.)

Figure 6.26 Selection of adults and children (age 10+) for imaging of the cervical spine.

(National Institute of Health and Clinical Excellence.)

When to involve the neurosurgeon

• Discuss the care of all patients with new, surgically significant abnormalities on imaging with a neurosurgeon (definition of ‘surgically significant’ to be developed by local neurosurgical unit and agreed with referring hospitals).

• Regardless of imaging, other reasons for discussing a patient’s care plan with a neurosurgeon include:

– persisting coma (GCS ≤8) after initial resuscitation

– unexplained confusion for more than 4 h

– deterioration in GCS after admission (pay greater attention to motor response deterioration)

– progressive focal neurological signs

– seizure without full recovery

– definite or suspected penetrating injury

– cerebrospinal fluid leak.

Transfer from secondary setting to neuroscience unit

Follow local guidelines on patient transfer and transfer of responsibility for patient care – these should be drawn up by the referring hospital trusts, neuroscience unit and local ambulance service. They should recognize that transfer would benefit all patients with serious head injuries (GCS ≤8), irrespective of the need for neurosurgery, but if transfer of those who do not require neurosurgery is not possible, ongoing liaison with the neuroscience unit over clinical management is essential.

• For emergency transfers, the patient should be accompanied by a doctor with appropriate training and experience and an adequately trained assistant.

• A child or infant should be accompanied by staff experienced in the transfer of critically ill children.

• The transfer team should be provided with a means of communicating with their base hospital and the neurosurgical unit during the transfer (a portable phone may be suitable providing it is not used within 1 m of medical equipment prone to electrical interference, such as infusion pumps).

• The multiply injured patient: consider the possibility of occult extracranial injuries, and do not transfer to a service unable to deal with other aspects of trauma.

Medical care during transfer

• In all circumstances: complete initial resuscitation and stabilization of the patient and establish comprehensive monitoring before transfer to avoid complications during the journey.

• Patient persistently hypotensive despite resuscitation: do not transport until the cause of hypotension has been identified and the patient stabilized.

Figure 6.27 Neurosurgical involvement.

Table 6.9 Intubation and ventilation

Circumstances	Action
Coma – GCS ≤8 (use paediatric scale for children)	Intubate and ventilate immediately
Loss of protective laryngeal reflexes
Ventilatory insufficiency: hypoxaemia (Pao2 <13 kPa on oxygen) hypercarbia (Paco2 >6 kPa)
Spontaneous hyperventilation causing Paco2 <4 kPa
Irregular respirations
Significantly deteriorating conscious level (1 or more points on motor score), even if not coma	Intubate and ventilate before the journey starts
Unstable fractures of the facial skeleton
Copious bleeding into mouth
Seizures
Ventilate an intubated patient with muscle relaxation and appropriate short-acting sedation and analgesia
Aim for:
Pao2 >13 kPa
Paco2 4.5–5.0 kPa
If clinical or radiological evidence of raised intracranial pressure, more aggressive hyperventilation is justified
Increase the inspired oxygen concentration if hyperventilation is used
Adult: maintain mean arterial pressure at ≥80 mmHg by infusing fluid and vasopressors as indicated
Child: maintain blood pressure at level appropriate for age

Guidelines for the Management of Severe Traumatic Brain Injury

Brain Trauma Foundation 2007

Recommendations

Blood pressure and oxygenation

A significant proportion of patients with traumatic brain injury (TBI) have hypotension and/or hypoxaemia, which increases morbidity and mortality. Hypotension (systolic BP <90 mmHg) and hypoxaemia (P_ao₂ <60 mmHg) must be avoided, or corrected immediately.

Hyperosmolar therapy

Mannitol is effective in lowering ICP in the management of TBI. The evidence for the use of hypertonic saline is not sufficient to make specific recommendations.

Prophylactic hypothermia

Some studies have shown that hypothermia may increase the chance of patients recovering from severe TBI to a Glasgow Outcome Score of 4 or 5. Hypothermia may have to be maintained for >48 h.

Deep vein thrombosis prophylaxis

Graduated compression stockings and low dose heparin reduce the risk of DVT, but the optimal dosing regimen and optimal time to start this therapy is unknown.

Intracranial pressure monitoring

The use of ICP monitoring in patients with severe TBI allows appropriate management of raised ICP, which is associated with improved outcome. Raised ICP pressure >20–25 mmHg requires treatment.

Cerebral perfusion thresholds

The optimal cerebral perfusion pressure (CPP) is unknown. Cerebral ischaemia generally occurs below 50–60 mmHg. A minimum of 60 mmHg is therefore recommended. No evidence that the use of pressors and volume expansion to drive CPP above 70 mmHg is beneficial.

Anaesthetics, analgesics and sedation

Barbiturates have been shown to control elevated ICP, but no evidence for any improvement in long-term survival. Important to avoid hypotension caused by many of these drugs.

Nutrition

Patients with severe TBI lose weight at a rate of 15% per week. Weight loss of >30% is associated with increased mortality in TBI patients. The optimal feeding regimen has not been established, but full feeding should be instigated by day 7.

Anti-seizure prophylaxis

Routine seizure prophylaxis is not indicated in patients >1 week post-injury.

Hyperventilation

Although hyperventilation may reduce raised ICP, it may also reduce cerebral blood flow to cause ischaemia. No good evidence to support hyperventilation following TBI.

Steroids

There is good evidence that high dose steroids worsen outcome in TBI and should therefore be avoided.

Trauma: Who Cares?

A Report of the National Confidential Enquiry into Patient Outcome and Death 2007

Summary

Road trauma accounts for over one-third of all deaths due to injury. In 2001–2003, there were (on average) 3460 traffic-related fatalities per annum in Great Britain. The incidence of severe trauma, defined as an Injury Severity Score (ISS) ≥16, is estimated to be four per million per week. Given that the UK population in mid-2003 was in the region of 59.5 million, there are approximately 240 severely injured patients in the UK each week.

Recommendations

Organizational data

There is a need for designated Level 1 trauma centres and a verification process needs to be developed to quality assure the delivery of trauma care (as has been developed in USA by American College of Surgeons).

Prehospital care

All agencies involved in trauma management, including emergency medical services, should be integrated into the clinical governance programmes of a regional trauma service.

Hospital reception

Trusts should ensure that a trauma team is available 24 h a day, 7 days a week. This is an essential part of an organized trauma response system.

A consultant must be the team leader for the management of the severely injured patient. There should be no reason for this not to happen during the normal working week.

Trusts and consultants should work together to provide job plans that will lead to better consultant presence in the emergency department at all times to provide more uniform consultant leadership for all severely injured patients.

Airway and breathing

The current structure of prehospital management is insufficient to meet the needs of the severely injured patient. There is a high incidence of failed intubation and a high incidence of patients arriving at hospital with a partially or completely obstructed airway. Change is urgently required to provide a system that reliably provides a clear airway with good oxygenation and control of ventilation. This may be through the provision of personnel with the ability to provide anaesthesia and intubation in the prehospital phase or the use of alternative airway devices.

Management of circulation

Trauma laparotomy is potentially extremely challenging and requires consultant presence within the operating theatre.

If CT scanning is to be performed, all necessary images should be obtained at the same time. Routine use of ‘top to toe’ scanning is recommended in the adult trauma patient if no indication for immediate intervention exists.

Head injury management

Patients with severe head injury should have a CT head scan of the head performed as soon as possible after admission and within 1 hour of arrival at hospital.

All patients with severe head injury should be transferred to a neurosurgical/critical care centre, irrespective of the requirement for surgical intervention.

Paediatric care

Each receiving unit should have up-to-date guidelines for children, which recognize the paediatric skills available on site and their limitations and include agreed guidelines for communication and transfer with specialized paediatric services within the local clinical network.

Transfers

There should be standardized transfer documentation of the patients’ details, injuries, results of investigations and management with records kept at the dispatching and receiving hospitals. Published guidelines must be adhered to and audits performed of the transfers and protocols.

Incidence of trauma and organization of trauma services

Given the relatively low incidence of severe trauma in the UK, it is unlikely that each individual hospital can deliver optimum care to this challenging group of patients. Regional planning for the effective delivery of trauma services is therefore essential.